This application describes a National Cooperative Natural Products Drug Dsicovery Group (NCNPDDG) to access natural products frrom highly productive, poorly studied or unstudied classes of cultured microorganisms and collected invertebrates from the marine environment. The overall goal of this program is to isolate, identify and develop anticancer agents with new structures, high selectivities toward cancer cells, and novel mechanisms of pharmacological action. The treatment of cancer evolves as new agents and strategies are combined with the development of more predictive models. Natural substances, historically a source of agents to treat human disease, are far from thoroughly investigated. In particular, the resources of the marine environment have scarcely been touched. We propose to examine marine sources for compounds that could be effective anticancer agents. The marine organisms investigated will include not only collected organisms such as sponges and molluscs but will also include marine microorganisms. This latter class, the microorganisms, has th potential of being a culturable resource. The Natural Products Laboratory Programs will conduct the search for marine organisms, crude extracts, and pure compounds. The Structural Analysis Laboratory Program will characterize the pure compounds. The Pharmaceutical Research and Development division of the Bristol-Myers Company will serve as the Cancer Pharmacology Program Laboratory. Bristol-Myers has a long history of developing anticancer agents and a throughly modern system of screens and predictive models.